Fasting Unmasks a Strong Inverse Association between Ghrelin and Cortisol in Serum: Studies in Obese and Normal-Weight Subjects

Abstract

Administration of ghrelin, the endogenous ligand for the GH secretagogue receptor, stimulates not only GH secretion but also appetite and food intake in humans. Endogenous ghrelin levels display a distinct circadian rhythm, which is reciprocal to that of insulin and presumed to be meal dependent and not associated with GH secretion. We tested the hypothesis that food deprivation could impact circadian serum ghrelin levels and unmask meal-independent regulatory mechanisms. Thirty-three young adults, subdivided according to gender and level of obesity, were studied with blood sampling every 3 h from 12-84 h of fasting. Serum ghrelin levels showed a marked diurnal rhythm with a nadir in the morning (0800 h), peak levels in the afternoon, and a gradual decline during the night. This pattern was preserved during the entire fasting period and was independent of gender and obesity. Mean 24-h ghrelin levels exhibited a small but significant decline during the fast (P < 0.001). As expected, GH secretion increased with fasting in lean subjects, and a gradual decline in insulin concentrations was observed in all subjects. Neither GH nor insulin showed any significant relationship to ghrelin. In contrast, serum cortisol exhibited a strong inverse temporal association with ghrelin (r = -0.79; P < 0.0001). In conclusion, our study yields no evidence that ghrelin stimulates GH release during fasting. As a novel finding, ghrelin appears to be related to cortisol. However, further studies are needed to elucidate the physiological mechanisms behind this relationship.

Gastric immunolocalization and plasma profiles of acyl-ghrelin in fasted and fasted-refed prepuberal gilts

“…However, Espelund et al (2005) in 84-h fasting humans did not find any significant relationship between ghrelin fluctuations and either insulin or glucose. In agreement with previous studies (Flanagan et al 2003) in humans, after refeeding insulin sharply increased while ghrelin returned to basal levels, thus demonstrating that postprandial hyperinsulinemia suppresses circulating ghrelin concentrations; these results are also in agreement with those of Broglio and colleagues (2004).…”

Effects of energy restriction on activity of the hypothalamo-pituitary-adrenal axis in obese humans and rodents: implications for diet-induced changes in body composition

“…Two studies have shown a decrease in circulating cortisol levels, after 48 h [42], or urinary cortisol levels after 3 days [43] of short-term severe energy restriction, while three other studies using short-term total fasting reported an increase in circulating cortisol [44 -46]. These latter studies involved an 84-h total fast [44] or 6 -11 days of starvation in obese men [45,46], and were found to increase circulating cortisol levels [44 -46] both total and unbound [46] -with no change [45] or only a slight increase [46] in total or free urinary cortisol. On balance, the majority of the studies (three out of five) that have investigated the effects of severe short-term energy restriction on circulating cortisol levels in obese humans have shown significant increases in this parameter.…”

Ghrelin Infusion in Humans Induces Acute Insulin Resistance and Lipolysis Independent of Growth Hormone Signaling

“…Plasma glucose was analyzed in duplicate using the glucose oxidase method (Beckman Instruments, Palo Alto, CA). Serum ghrelin (total levels) was measured in duplicate by an in-house assay (12). Serum GH, cortisol, and insulin were analyzed with a double monoclonal immunofluorometric assay (Delfia; Perkin Elmer, Wallac Oy, Turku, Finland).…”